In order to cause disease, pathogenic bacteria require specialized means to sense the various microenvironments presented to them in the context of a host and then to regulate the systems required for establishment, persistence, growth, and induction of the pathologies associated with infection. The example presented in this chapter focuses on one such system utilized by Bacillus anthracis during anthrax infections, iron acquisition. Recently, research focused on the acquisition of one such nutrient essential for successful anthrax infections, iron, has come to the fore. The chapter summarizes the various mechanisms used by B. anthracis for obtaining iron, reviews the relative impact of each of these mechanisms on a successful anthrax infection, and presents the transcriptome regulated by low concentrations of iron. Once inside the bacterial cytoplasm, iron is released from heme when the heme monooxygenase, IsdG, breaks down the molecule. Siderophores are high-affinity iron-chelating molecules that are secreted into the extracellular environment, where they scavenge iron from a variety of host sources. B. anthracis produces two siderophores, bacillibactin and petrobactin. Petrobactin is made up of one central citrate flanked by two spermidine molecules, each with terminal dihydroxybenzoic acid residues. Consequently, molecules that inhibit or block iron acquisition, related membrane transport processes, or bacterial iron-based regulation, in general, may prove to be effective new medical counter-measures against anthrax and related infections. It is predicted that as more defined details of the genes, proteins, factors, and mechanisms that regulate iron metabolism become understood, reasonable countermeasure targets will be identified.

The three primary mechanisms of iron acquisition in Bacillus anthracis. The pathways for iron acquisition using heme (left), petrobactin (center), and bacillibactin (right) are shown. The structure of each molecule is shown above its respective transport system (red residues interact directly with iron). Iron-binding molecules are represented by red squares (heme), yellow crescents (petrobactin), and maroon triangles (bacillibactin). All known components of these three specific transport systems are represented. Specific components and functions of each iron acquisition system are discussed within the text. Representations of the genes in the biosynthetic operons for petrobactin and bacillibactin are shown beneath their respective transport systems. doi:10.1128/9781555818524.ch16f1

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Figure 1

The three primary mechanisms of iron acquisition in Bacillus anthracis. The pathways for iron acquisition using heme (left), petrobactin (center), and bacillibactin (right) are shown. The structure of each molecule is shown above its respective transport system (red residues interact directly with iron). Iron-binding molecules are represented by red squares (heme), yellow crescents (petrobactin), and maroon triangles (bacillibactin). All known components of these three specific transport systems are represented. Specific components and functions of each iron acquisition system are discussed within the text. Representations of the genes in the biosynthetic operons for petrobactin and bacillibactin are shown beneath their respective transport systems. doi:10.1128/9781555818524.ch16f1